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Re: Re: Re: "Question About Magic Johnson"
Mar 31, 2004

Dear Dr. Pierone, Thank you (again) for responding to my long question.

There is no comparison between early treatment (within six to eighteen months of initial infection) and treatment in patients with CD4+ nadirs (low point) near 200 cells/mml. Yes, I too know of a few people who had CD4+ T cells hovering around 50 cells/mml, then received HAART and have had CD4+ T cells in the 700 to 900 range for the past three years. I doubt that they could have achieved this on a regimen of every substance that I recently mentioned.

But, I'm NOT advocating clinical trials of these substances in sick HIV+ patients who have allowed HIV to destroy their immune systems before starting treatment. Cohorts of sick HIV+ patients, with poorly functioning immune systems are (almost) the ONLY cohort that is ever studied IN SIGNIFICANT NUMBERS, LONG-TERM, in HIV clinical trials. Healthy, non-drug-naive HIV+ patients are ignored. Therefore, we don't have ANY clinically significant data from this important group of HIV+ patients to rule-in OR rule-out the use of "squeezing coconuts" (monolaurin), and the other compounds I mentioned, in healthy HIV+ patients with strong immune systems.

The Aquitaine cohort (1996-1998) is the only exception that I am aware of. And that was NOT a recently infected cohort. That cohort was somewhere between recently infected and AIDS. "Moderately advanced" was the term used to describe that cohort.

"selenium, licorice root (Glycyrrhiza glabra), coconut oil (Monolaurin), aspirin, and NAC", are ALL "purified" and "mass produced", and sold at great profit I might add.

I am not aware of any clinical trial data that supports your claim that healthy, recently infected, treatment naive, HIV+ patients (this is important) who have viral loads between (say) 2,000 and 20,000 OFF ALL TREATMENT are at any risk of disease progression (this is MOST important) IF they receive treatment that lowers their viral load to near 50 copies/mml.

Bruce Walker, MD's recent clinical trial, that treated patients early, then took them off treatment and watched HIV destroy their adaptive and innate immune systems, told us that HIV will continue to be destructive, no matter how strong an individual's immune system is. But, then, we already knew that.

Your colleague, Mark Holodniy, M.D., F.A.C.P., C.I.C., co-authored both a poster (9th CROI 2002) and a follow-up paper, "Low Levels of Adherence Do Not Increase Risk of HIV Drug Resistance", that does not appear to support the claim that healthy HIV+ patients with strong adaptive immune systems will do poorly on a dual-drug treatment regimen that lowers viral load to (say) near 50 copies/mml.

The immune systems of most people, who receive early treatment, preforms the major amount of clearance of HIV - not their drugs. And because their adaptive immune system has SOME ability to follow HIV's mutations, AND because their innate immune system clears HIV from infected cells regardless of whether it is "resistant" or not, the goal of early treatment - with the LEAST toxic and LEAST powerful treatment regimen - should be preserving the functionality of the immune systems. Over-medicating eary treated HIV+ patients with HAART might cause MORE problems (over the long term) than it prevents.

Judging from my own personal experience with early treatment, and the experience that two other people I know who also received early treatment, delaying treatment until the immune system is destroyed, as opposed to running clinical trials to find the Least Toxic and Least Powerful treatment necessary to preserve the adaptive and innate immune systems, seems negligent.

Kind regards,

Tom

Response from Dr. Pierone

Correct me if I am wrong, but I think the spirit of your suggested treatment construct is to hit early in HIV-infected patients with relatively low viral loads in an attempt to prevent immune system loss from unbridled HIV replication. But importantly, attempt to bring HIV replication under control with combinations of non-toxic antiretrovirals, preferably 'natural source' agents rather than medications synthesized in a laboratory. (when you say least powerful regimen, my assumption is that you desire enough activity to suppress viral replication).

If this is an accurate representation of your idea for research into an alternative treatment strategy for HIV infection, then we really have little disagreement.

My personal view is that this is the future of HIV treatment will entail exactly this - hit early, but with simple and clean combinations of non-toxic agents to stop viral replication and prevent immune deficiency.

Perhaps the main difference in our future view of HIV treatment is that I believe these non-toxic, targeted, and extremely potent agents will be the product of rational drug development and design. I realize that there are some chemicals from natural sources that have activity against HIV and we will continue to unearth new ones. But I don't think that antiretroviral agents from natural sources can hope to match the astonishing and radical transformation that is occurring in the realm of targeted drug discovery.

The revolution in molecular biology is producing new targets for drugs together with new techniques to specifically design and synthesize agents for those newly discovered targets. The field is moving forward at lightening pace. Although natural source molecules will be added to existing chemical libraries, the ultimate development of new agents will not be left to chance. Instead, a blueprint for a candidate antiretroviral agent will be developed based on specific attributes designed to block or augment a molecular target the so called "magic bullet".

These new agents will be tested first as short course monotherapy to prove potency and safety. Then they will be used in combination therapy in sick patients, but as experience mounts, the safest agents will migrate into the types of patients that you describe healthy, newly infected patients with low viral loads.

I guess that my fervent optimism and belief in scientific progress is reflected in this view. The early technological solution to AIDS protease inhibitor-centered HAART, although successful in improving and extending life, was rough and toxic. The future solution will, I believe, be clean, elegant, and easy to live with.



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